Pseudoephedrine has been used in combination with cetirizine for treating perennial or seasonal allergic diseases including nasal obstruction, sneezing, and rhinorrhea. Commercially available complex formulations are ZYRTEC PLUS (UCB Pharma) and KOSSAK (Hanmi Pharm Co. Ltd), in which the pseudoephedrine shows a sustained release rate over 10 to 12 hours while the cetirizine shows a fast release within 2 hours.
The pseudoephedrine has an in vivo ranging from 5 to 7 hours and is orally administered 3 or 4 times/day in divided doses. Therefore, the pseudoephedrine must be prepared in the form of a sustained release formulation when used in combination with a single dose drug such as cetirizine for the sake of the patient's convenience.
Various complex compositions comprising pseudoephedrine and cetirizine have been developed. For example, Korean Patent Pub. No. 2009-26140 discloses a bi-layer tablet composed of a pseudoephedrine segment which contains pseudoephedrine and hydroxypropylmethylcellulose (HPMC) and a cetirizine segment containing cetirizine, lactose, and microcrystalline cellulose. However, the bi-layer tablet can not be prepared using a conventional monolayer tablet machine, but the use of a special tablet press machine which is capable of pressing each of granular forms of the drugs into a bi-layer tablet is required.
Further, Korean Patent Pub. No. 2006-2235 discloses a sustained-release formulation which is prepared by a method comprising the steps of: coating white sugar with pseudoephedrine HCl; coating the pseudoephedrine HCl-coated white sugar with ethylcellulose which is a coating layer-forming agent for controlling sustained release of the pseudoephedrine to obtain a sustained release core; and coating the sustained release core with pseudoephedrine and cetirizine. This formulation is composed of a part that enables both a fast release and a sustained release of pseudoephedrine and the part that allows a fast release of cetirizine.
Levocetirizine, an isomer of cetirizine, is a histamine H1 receptor antagonist, and it is used as an antihistamine agent, which is marketed in Korea under the trade name of XYZAL™ (UCB pharma), which is a fast release drug formulation having a releasing rate of 80% or more within 30 min. Levocetirizine is also used in combination with pseudoephedrine for treating perennial or seasonal allergic diseases including nasal obstruction, sneezing, and rhinorrhea.
However, there has been a need for developing a pseudoephedrine-levocetirizine containing complex composition which has an improved levocetirizine releasing rate and does not show a delayed release behavior even after a long storage time.